Project Summary: We previously demonstrated that the patient and graft survival rates for HIV+ to HIV+ kidney transplants are comparable to rates seen in other HIV+ transplant recipients. We also showed that these transplants do not result in sustained HIV superinfection despite presence of a detectable donor viral inoculum in these recipients, alleviating one of the major concerns with these surgeries. This proposal aims to expand on these novel findings by initially exploring how the immune modulators these patients receive may affect the HIV latent viral reservoir, which is the primary hurdle in the search for an HIV cure. In addition, we and others have observed a possible increased risk of rejection in HIV+ kidney transplant recipients in general. Therefore, we have partnered with the HIV transplant and pathology groups at UCSF, as well as a team of other collaborators from the US, Spain, and South Africa, to examine the role of several components of the immune response associated with organ rejection. We will also utilize this diverse team of experts in HIV infectious disease, pathology, and transplantation to increase clinical and laboratory support for transplantation services in underserved areas in South Africa, thereby increasing availability of these life- saving transplants. The results of this study will have a direct and immediate influence on transplant clinical practice in South Africa and the US. Additionally, our study provides an opportunity to answer multiple fundamental biological questions surrounding HIV cure research and HIV related organ rejection.